Using Quantum Chemical Methods, we propose to continue systematic investigation of electronic and conformational properties of opiate narcotics and their interaction with model receptor sites. The aim of these studies will be further understanding of the molecular properties determining analgesic activity, antagonism and possibly related to tolerance, dependence and specific side-effects. Calculations will also be made of newly discovered endogenous opiates (endorphins) to see how they can be structurally related to known classes of opiates. To these ends, the specific projects chosen for investigation are: 1) A series of 2'OH 5,9-dimethyl 6,7-benzomorphan with N-furylmethyl and related substituents which produce a range of agonist and antagonists, some with clinical promise. 2) A series of 2'OH 2-methyl, 5,9-dialkyl 6,7-benzomorphans which include potent agonists with weak antagonism and low physical dependence capacity. 3) N-methyl, N-allyl and N-methyl cyclopropyl derivatives in the potent oripavine series. 4) N-alkyl ketobemidone analogues with extensive in vivo and in vitro data contrasting activities relative to meperidines and prodines. 5) N-alkyl derivatives of beta-meperidines with agonist and antagonist activity. 6) comparison of fused ring structural differences with changes in agonist-antagonist properties of the same N-substitutients of 3,4 and 5 fused ring opiates. 7) Opiate interactions with model anionic receptors such as sulfate, phosphate and carbonate esters. 8) Conformational studies of enkephalins to compare with exogenous opiates.